This proposal focuses on development of technology that is suited for both ultra-high resolution animal imaging systems and other high resolution applications such as human breast and head imaging. An integral part of our work to date is the development of a highly modular approach to the detectors and supporting electronics. This approach assures that imaging resources built using the technology can easily adapt to the changing demands of the biological research. In the previous funding period cost effective designs of detector modules, electronics, and reconstruction algorithms to provide ~ 1mm3 volume resolution were completed. In this renewal application, we propose to further develop detector modules, electronics, and reconstruction algorithms to support a depth-of-interaction design (dMiCE) that is an extension of our MiCES system designs. A major focus is on cost effective designs, and therefore our dMiCE module is based on a single-ended readout of light with light sharing between pairs of crystals to provide the depth-of-interaction (DOI) information. The proposal includes a careful optimization of light sharing techniques; investigation of multi-anode photomultiplier tubes (PMTs), position sensitive PMTs, and pixelated and position sensitive avalanche photodiodes as photoreceptors; new electronics designs moving essentially all pulse processing (integration, pileup correction/prevention, timing pickoff) into field programmable gate arrays (FPGAs); and extensions of our reconstruction algorithms to support DOI. The overall goal is to achieve spatial resolutions < 1.2 mm with sensitivity in a typical small animal configuration of > 15%. The effort will also include the development of maximum likelihood estimators for crystal-of-interaction and depth-of-interaction in segmented crystal module designs as well as better methods for optimization of our DOI approach. An important aspect of the work is to extend the DOI designs to investigate potential applications in time- of-flight (TOP) systems by both implementing FPGA based electronics that can provide timing resolutions of ~300 ps (thebest values reported for current scintillators/PMTs for practical tomograph designs) and utilize DOI based TOP correction to improve the overall timing resolution of potential TOP scanner designs. The net result of our work will be contributions to the general knowledge of options for detector and electronics design for high-resolution detector systems as well as insight into methods to optimize TOP performance for different detector module designs.